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Glypican 3 (GPC3)

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 21 November 2011, last major update November 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.


● Heparan sulfate proteoglycan; mutated in Simpson-Golabi-Behmel syndrome (National Institutes of Health)


● Cytoplasmic and membranous staining

Uses by Pathologists

● (1) Distinguish hepatocellular carcinoma (usually GPC3+) from non malignant liver (GPC3-) as part of a panel (Am J Clin Pathol 2008;130:219, Am J Surg Pathol 2008;32:433), but cirrhotic nodules may show focal strong staining (Mod Pathol 2008;21:1011)
● (2) Distinguish hepatocellular carcinoma from other primary and metastatic hepatic lesions by FNA (Mod Pathol 2008;21:626)
● (3) Distinguish ovarian yolk sac (GPC3+) from embryonal carcinoma (GCP3-) as part of a panel (Hum Pathol 2010;41:716)

Micro images

Gestational endometrium

Staining in cirrhotic nodules (occurs occasionally)

Hepatic adenoma (negative)


Hepatocellular carcinoma

Figures e/f: fibrolamellar and hepatocellular carcinoma

Figures c1/c2: CNS yolk sac tumor

Left: ovarian yolk sac tumor; right: ovarian clear cell adenocarcinoma

Placental site trophoblastic tumor and other uterine/cervical lesions

Cytology images

Hepatocellular carcinoma

Positive staining - nontumors

● Endometrium-gestational; hepatitis C with high grade activity (>90%, Hum Pathol 2008;39:209)

Positive staining - tumors

● Hepatocellular carcinoma (40-65%), fibrolamellar carcinoma (Mod Pathol 2010;23:1180), hepatoblastoma (>90%, Hum Pathol 2008;39:224); also undifferentiated embryonal sarcoma and mesenchymal hamartoma of liver (Hum Pathol 2011 Sep 19 [Epub ahead of print)
● Lung-squamous cell carcinoma (54%), testicular nonseminomatous germ cell tumors (52%), liposarcoma (52%, Am J Clin Pathol 2008;129:899)
● Ovarian (>90%) and extragonadal (>90%) yolk sac tumors (may be focal, Am J Surg Pathol 2009;33:1529), ovarian choriocarcinoma, teratomas (variable, immature > mature, Am J Clin Pathol 2008;130:224), ovarian clear cell carcinoma (Mod Pathol 2009;22:824), placental site trophoblastic tumor (Diagn Pathol 2010;5:64)
● Rhabdomyosarcomas (35%), but not other sarcomas (J Clin Pathol 2011;64:587)

End of Stains > Glypican 3

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